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Query: UMLS:C0015672 (fatigue)
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Primary pulmonary hypertension carries a poor prognosis, with a 5 year survival rate of less than 25%. However, a previous study of more than 100 patients with tissue-proved primary pulmonary hypertension suggested that antithrombotic therapy may have a beneficial effect on survival, especially in patients with the thromboembolic type of primary pulmonary hypertension. This report describes a 54 year old white man with primary pulmonary hypertension of the thromboembolic type (proved by right upper lobe lung biopsy) who, after long-term antithrombotic therapy, showed resolution of symptoms of dyspnea and fatigue, regression of electrocardiographic signs of right ventricular hypertrophy and regression of elevated pulmonary artery pressure. Base-line cardiac catheterization in January 1982 revealed elevated pulmonary artery pressure (104/37 mm Hg) and pulmonary vascular resistance (14.6 units/m2) that did not decrease with 100% oxygen or intravenous hydralazine (12 mg). The patient was treated with warfarin and dipyridamole, 100 mg four times daily. The most recent cardiac catheterization in January 1984 revealed a pulmonary artery pressure of 50/15 mm Hg and a pulmonary vascular resistance of 8.7 units/m2. It is believed that this is the first report of regression of the symptoms and signs of biopsy-proved primary pulmonary hypertension. In view of the lack of a response to vasodilators in 1982, it is suggested that antithrombotic therapy is partially responsible for the improvement of this patient.
J Am Coll Cardiol 1986 Jan
PMID:Regression in thromboembolic type of primary pulmonary hypertension during 2 1/2 years of antithrombotic therapy. 394 Dec 8

Although Doppler echocardiography is useful in the assessment of left ventricular function at rest, little information is available on the application of this technique during exercise. Consequently, Doppler aortic flow studies were performed in 17 young normal subjects during and after supine bicycle exercise. The purposes of the study were to determine the feasibility of recording Doppler aortic flow velocity with a suprasternal notch transducer during exercise and to assess the changes in normal aortic flow velocity parameters during exercise and early recovery. Each subject exercised until fatigue; mean duration of exercise was 10 minutes. Heart rate increased from a mean of 69 beats/min at control to 159 beats/min at peak exercise. On average, aortic peak flow velocity increased by 45% from control, reaching its maximum at 2 minutes after exercise. Ejection time decreased by 34% during exercise, being shortest at peak exercise. Heart rate, peak flow velocity and ejection time had not returned to normal by 10 minutes after exercise. Aortic flow velocity integral (a relative measure of stroke volume) decreased by 10% at peak exercise (p less than 0.05) compared with control, but had returned to control at 2 minutes after exercise. Despite mild aliasing, increased spectral dispersion, faster heart rates and increased respiratory rate during maximal exercise, aortic flow velocity measurements could be recorded using the suprasternal technique. These baseline Doppler exercise data should be useful in further studies of exercise hemodynamic changes in patients with heart disease.
Am J Cardiol 1986 Feb 01
PMID:Studies of Doppler aortic flow velocity during supine bicycle exercise. 394 24

This study was conducted to determine if the limiting symptom in patients with coronary artery disease (CAD) influenced the pattern of oxygen consumption (VO2) over the final 90 seconds of a maximal exercise test. The pattern was classified according to the presence or absence of a plateau. Twenty-six normal persons and 55 patients with CAD were studied. They rated the severity of fatigue, dyspnea and angina at end exercise using the Borg scale and designated which symptom was the limiting factor. A plateau of VO2 over the final 90 seconds of exercise was observed in 77% of normal subjects and patients with CAD. Eighty percent of patients limited by angina achieved a plateau. In normal subjects and patients with CAD, peak VO2 was more reproducible than the pattern of VO2 over the final 90 seconds of exercise. There were no differences in the cardiac responses to exercise at maximal effort between patients who achieved a plateau of VO2 and those who did not. These results indicate that the limiting symptom of exercise, even angina pectoris, does not influence the ability to exercise maximally. Therefore, the peak value of VO2 during symptom-limited treadmill exercise is a valid measure of maximal cardiovascular capacity irrespective of the limiting symptom or the pattern of VO2 in the final 90 seconds of exercise.
Am J Cardiol 1986 Mar 01
PMID:Effects of the limiting symptom on the achievement of maximal oxygen consumption in patients with coronary artery disease. 395 34

The effect of selective and nonselective beta-adrenoceptor blockade on the thermoregulatory responses of 11 physically active, healthy, young adult men was studied during 2-hour block-stepping in heat. The trial consisted of 3 periods of 6 days each during which propranolol (160 mg/day), atenolol (100 mg) or matching placebo was administered in a randomized, double-blind crossover fashion. Propranolol and atenolol induced similar, significant (p less than 0.001) increases in subjective ratings of perceived exertion. The mechanism of this increased fatigue was not evident from the documented alterations in serum electrolyte, blood glucose and blood lactate levels or ventilatory parameters. Propranolol did, however, induce a postexercise delayed serum-potassium reversion. Although rectal and mean skin temperature responses were essentially unaltered by beta-adrenoceptor blockade during block-stepping, an increased total sweat loss was observed with propranolol (p less than 0.01 versus placebo) and to a lesser degree with atenolol (p = not significant versus placebo). This indicates that persons receiving beta-adrenoceptor blockers have an increased need to adhere to a strict fluid-replacement regimen during exercise. This potentially adverse response was minimal with atenolol in contrast to propranolol, and this in turn suggests the use of beta1-selective adrenoceptor blockers during prolonged exercise when adequate fluid replacement is not possible.
Am J Cardiol 1985 Apr 26
PMID:Effect of selective and nonselective beta-adrenoceptor blockade on thermoregulation during prolonged exercise in heat. 399 52

This study attempts to define cardiac performance at rest and during exercise in patients with untreated thyrotoxicosis. We studied 7 women and 3 men, aged 23 to 59 years (40 +/- 10, mean +/- standard deviation [SD]) and compared the results with those obtained in 12 normal subjects. In patients with thyrotoxicosis, the rhythm was sinus and the only untoward symptom was palpitations; the resting electrocardiographic results were normal in 8 patients and showed left ventricular hypertrophy in 2 patients; the left ventricular ejection fraction and volumes (measured by radionuclide ventriculography) were normal at rest. During exercise, 1 patient had dyspnea and 7 had leg fatigue; 2 were asymptomatic. Also, 7 patients had greater than or equal to 5% increase in left ventricular ejection fraction, 2 had no change, and 1 had a decrease. In all 10 patients, the exercise ejection fraction was greater than or equal to 60%. All normal subjects had a greater than or equal to 5% increase in ejection fraction during exercise. There were no significant differences at rest between patients with thyrotoxicosis and normal subjects in blood pressure, ejection fraction, end-diastolic volume, stroke volume, end-systolic volume, or cardiac output, but the heart rate was significantly higher in patients with thyrotoxicosis (91 +/- 10 versus 80 +/- 12 beats/min, p less than 0.05). During exercise, there were no significant differences between patients with thyrotoxicosis and normal subjects in blood pressure, end-diastolic volume, stroke volume, end-systolic volume, or cardiac output. The exercise ejection fraction was significantly lower in patients with thyrotoxicosis than in normal subjects (68 +/- 10% versus 75 +/- 4%, p less than 0.05). Cardiac performance is normal at rest in patients with thyrotoxicosis, but during exercise abnormal left ventricular reserve occurs in some patients.
Am J Cardiol 1983 Jan 15
PMID:Cardiac performance in thyrotoxicosis: analysis of 10 untreated patients. 621 43

Our previous work showed that myosin phosphorylation decreased the ATPase activity of skeletal muscle myofibrils that were lightly fixed with glutaraldehyde. The fixation process prevented sarcomere shortening and destruction of the ordered filament array upon the addition of ATP. We have now extended these results to myofibrils prepared from hearts of rabbits, dogs and rats. Myofibrils were phosphorylated by incubation with myosin light chain kinase, calmodulin and either ATP-gamma s or ATP, for 15 minutes at 25 degrees C. The extent of myosin light chain phosphorylation was 50% to 80%. The ATPase activity of unphosphorylated myofibrils was not altered by reaction with 0.01% glutaraldehyde for 5 minutes at 0 degrees C, and the ATPase activity of unfixed myofibrils was not changed by phosphorylation. However, phosphorylation decreased the ATPase activity of fixed myofibrils by 50%. The effect on myocardial myofibrillar ATPase activity of phosphorylation was similar in the three animal species. These results suggest that in both skeletal and cardiac muscle, myosin phosphorylation decreases the rate of cross-bridge cycling resulting in decreased energy expenditure. It also appears that the effect of myosin light chain phosphorylation on ATPase activity requires an ordered myofilament structure.
J Mol Cell Cardiol 1984 Jul
PMID:Myosin phosphorylation decreases the ATPase activity of cardiac myofibrils. 623

Ninety-two patients with heart failure refractory to digitalis and diuretic therapy had captopril (n = 50) or placebo (n = 42) added to their therapeutic regimen in a randomized, double-blind trial. During a 2 week dosage titration period, one captopril-treated patient died of an intracerebral hemorrhage. Over the remaining 10 week evaluation period, 1 captopril-treated patient (2%) was excluded from the study because of treatment failure as compared with 12 discontinuations (4 deaths and 8 failures [29%]) among the placebo group (p less than 0.001). Eighty percent of patients in the captopril group exhibited some degree of clinical improvement, whereas only 27% in the placebo group did so (p less than 0.001). The therapeutic advantage of captopril over placebo was evidenced by a mean improvement of 0.52 (2.8 +/- 0.1 to 2.3 +/- 0.1) in the New York Heart Association functional class value as compared with 0.03 (2.9 +/- 0.1 to 2.8 +/- 0.1) with placebo (p less than 0.0001). There was a 24% mean increase in exercise tolerance with captopril (495 +/- 22 to 614 +/- 27 seconds) as compared with 0.4% with placebo (480 +/- 28 to 483 +/- 43 seconds) (p less than 0.01); the captopril group had an increase in the ejection fraction from a mean baseline value of 0.19 +/- 0.02 to 0.22 +2- 0.02 as compared with 0.19 +/- 0.02 to 0.18 +/- 0.002 (p less than 0.05) in the placebo group. A cohort analysis revealed that improvement in exercise tolerance with captopril was gradual and progressive throughout the 12 weeks. Improvement in specific symptoms of heart failure, that is, dyspnea, fatigue and orthopnea, and the reduction of edema also were greater in the captopril-treated patients (p less than 0.05 to p less than 0.001). Captopril therapy was well tolerated, although symptomatic hypotension after the first dose caused withdrawal of three patients (3%) from the study. It was concluded that captopril is an effective adjunctive treatment to digitalis and diuretic drugs for patients with refractory heart failure.
J Am Coll Cardiol 1983 Oct
PMID:A placebo-controlled trial of captopril in refractory chronic congestive heart failure. Captopril Multicenter Research Group. 635 Apr 1

The mitral apparatus is a complex structure composed of several components, each of which can be affected by a variety of diseases, resulting in mitral regurgitation. The physiologic consequences of mitral regurgitation include reduced forward stroke volume; increased left atrial volume and pressure; and reduced resistance to left ventricular ejection. The latter explains why indices of systolic left ventricular function (ejection fraction) are often increased early in the course of mitral regurgitation. With the insidious development of mitral regurgitation, the left atrium dilates to accommodate the increase in volume, thereby reducing the atrial pressure. However, with the acute development of mitral regurgitation into a nondilated left atrium, pressure rises rapidly, producing pulmonary edema. The predominant clinical symptoms in chronic mitral regurgitation of dyspnea and fatigue result from pulmonary venous hypertension and low cardiac output. The cardinal physical finding is a mitral systolic murmur. Since the murmur can assume various configurations, the most reliable way to establish its correct origin is by bedside physiologic maneuvers. Typically, in the beat following a premature contraction or after a long pause during atrial fibrillation, the murmur of mitral regurgitation is unchanged in intensity, but murmurs due to left ventricular outflow obstruction increase. Also, isometric handgrip exercise increases the intensity of the murmur and a Valsalva maneuver decreases it during the strain phase. Echocardiography is the most useful noninvasive technique for evaluating patients with mitral regurgitation. Visualization of the mitral apparatus may establish the etiology of regurgitation, and measurement of left atrial size and left ventricular size and performance is useful for assessing the functional significance of the lesion. Doppler echocardiography can establish the diagnosis of mitral regurgitation in difficult cases with multi valve disease and can estimate the severity of the regurgitation. Cardiac catheterization and angiography are usually reserved for the patient being considered for valvular surgery. The natural history of chronic mitral regurgitation is characterized by slowly progressive symptoms, and often the onset of disabling symptoms is the result of irreversible left ventricular dysfunction. Medical therapy consists of digitalis, diuretics, and vasodilators for symptomatic patients. When symptoms occur despite this therapy, valvular surgery should be considered before left ventricular function becomes abnormal.
Curr Probl Cardiol 1984 May
PMID:Mitral valve regurgitation. 637 82

The cause of exercise intolerance in congestive heart failure is unclear. Hemodynamic and ventilatory responses were measured during symptomatic maximal upright bicycle exercise in 28 patients with chronic severe left ventricular failure who achieved a maximal oxygen uptake of only 12 +/- 4 ml/min/kg (+/- standard deviation). All patients reached anaerobic metabolism as the respiratory exchange ratio rose and arterial pH fell significantly. Pulmonary capillary wedge pressure increased from 20 +/- 10 mm Hg at rest to 38 +/- 9 mm Hg at peak exercise and cardiac index increased from 2.51 +/- 0.73 to 4.54 +/- 1.65 liters/min/m2 (both p less than 0.001). Systemic vascular resistance decreased, but pulmonary vascular resistance did not change during exercise. Despite the marked pulmonary venous hypertension at peak exercise, blood gases were unchanged (PaO2, 96 +/- 15 mm Hg; PaCO2, 35 +/- 7 mm Hg). Systemic arterial oxygen content increased from 16 +/- 2 to 17 +/- 2 vol% (p less than 0.01). Changes in pulmonary capillary wedge pressure did not correlate with changes in arterial oxygen content. Results were similar whether patients were limited by dyspnea or fatigue. Thus, exercise intolerance in patients with severe left ventricular failure is associated with marked elevation of pulmonary capillary wedge pressure and anaerobic metabolism without hypoxemia or altered carbon dioxide tension. These findings suggest that exercise ability in congestive heart failure is more dependent on cardiac output than on ventilatory consequences of pulmonary congestion.
Am J Cardiol 1984 Jan 01
PMID:Relation between hemodynamic and ventilatory responses in determining exercise capacity in severe congestive heart failure. 641 73

The direct smooth muscle vasodilator hydralazine has been used to treat exertional fatigue in patients with chronic heart failure. However, prior studies suggest that arteriolar vasodilators such as hydralazine may actually impair nutritive flow to working skeletal muscle by interfering with the distribution of blood flow within muscle. To investigate this possibility, tension development and metabolism were measured in nine vascularly isolated gracilis muscle preparations perfused at 90 mm Hg and stimulated to contract progressively at rates of 1, 3 and 6/s with each stage lasting 3 minutes. Studies were then repeated after 30 minutes of intraarterial hydralazine (0.02 to 0.12 mg/min). At rest, hydralazine decreased mean vascular resistance (+/- SEM) from 15.1 +/- 1.4 to 8.6 +/- 0.9 X 10(2) units (p less than 0.001) and increased blood flow from 6.4 +/- 0.7 to 11.4 +/- 1.2 ml/min (p less than 0.001), but did not change oxygen consumption (VO2) control, 18 +/- 1 versus hydralazine, 17 +/- 2 microliter/min). Hydralazine also decreased vascular resistance and increased flow at a contraction rate of 1/s, but not at 3 and 6/s. Hydralazine had no effect on maximal VO2 (control, 254 +/- 18 versus hydralazine, 236 +/- 19 microliter/min), maximal developed tension (control, 353 +/- 90 versus hydralazine, 334 +/- 74 kg X min) or the response in venous lactate (control, 20.6 +/- 2.3 versus hydralazine, 18.1 +/- 2.0 mg/dl). Hydralazine also did not change muscle metabolism and function at contraction rates of 1 and 3/s. These data suggest that hydralazine does not adversely affect nutritive flow to working skeletal muscle.
J Am Coll Cardiol 1984 Sep
PMID:Effect of hydralazine on nutritive flow to working canine gracilis skeletal muscle. 647 Mar 32


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